SINGLE CELL RESOLUTION OF THE ADULT ZEBRAFISH INTESTINE UNDER CONVENTIONAL CONDITIONS, AND IN RESPONSE TO AN ACUTEVIBRIO CHOLERAEINFECTION

Abstract

ABSTRACTVibrio choleraeis an aquatic bacterium that primarily infects the gastrointestinal tract, causing the severe and potentially deadly diarrheal disease, cholera. Despite the impact ofVibrioon global health, our understanding of host mucosal responses to the pathogen at the site of infection remains limited, highlighting a critical knowledge gap that must be addressed to develop more effective prevention and treatment strategies. Using a natural infection model, we combined physiological and single-cell transcriptomic studies to characterize adult zebrafish guts raised under conventional conditions and after a challenge withVibrio. We discovered thatVibriocauses a mild mucosal immune response characterized by T cell activation and enhanced antigen capture in the epithelium. Additionally, we discovered thatVibriosuppresses host interferon signaling, and that ectopic activation of interferon significantly alters the course of infection. Notably, we also found that the adult zebrafish gut shares many similarities with mammalian counterparts, including the presence of previously undescribed Best4+ cells, tuft cells, and a population of basal cycling cells. These discoveries provide important insights into host-pathogen interactions and emphasize the utility of zebrafish as a natural model ofVibrioinfection.